Molecular epidemiology of malaria in Cameroon. XII. In vitro drug assays and molecular surveillance of chloroquine and proguanil resistance.

Abstract

Abstract. Chloroquine-proguanil combination is one of the options for chemoprophylaxis. The rapid evolution of drug resistance status requires a constant upgrade of epidemiologic data. Due to various difficulties in conducting prospective clinical studies on the prophylactic efficacy of the drug combination, especially in highly chloroquineresistant zones, in vitro drug sensitivity assays and specific molecular markers for chloroquine (Plasmodium falciparum chloroquine-resistance transporter, pfcrt) and cycloguanil (a biologically active metabolite of proguanil; dihydrofolate reductase, dhfr) resistance were evaluated as an alternative approach in this study. Of 116 isolates, 62 (53.4%) were doubly resistant in vitro to chloroquine (IC 50 Ն 100 nM) and cycloguanil (IC 50 Ն 15 nM). Likewise, 62 of 118 isolates (52.5%) carried both the mutant Thr-76 pfcrt allele and at least one dhfr mutant allele (1 with a single Asn-108 allele, 8 with double Arg-59 and Asn-108 mutations, and 53 with triple Ile-51, Arg-59, and Asn-108 mutations). The in vitro drug response corresponded with the presence or absence of key mutation(s) in the pfcrt and dhfr genes. These results suggest the high proportion of P. falciparum isolates in southern Cameroon that may not respond to chloroquineproguanil combination.

Risk Factors for Placental Malaria and Its Effect on Pregnancy Outcome in Yaounde, Cameroon

“…In the late 1990s, increasing drug resistance not only to CQ, but also to pyrimethamine, proguanil, and probably amodiaquine were reported in Yaounde. [35][36][37] Accordingly, intermittent preventive treatment with sulfadoxine-pyrimethamine in pregnant women has been adopted, but sulfadoxine-pyrimethamineresistant strains are present in Yaounde, 35 making the efficacy of the new policy uncertain.…”

Malaria in Pregnant Cameroonian Women: The Effect of Age and Gravidity on Submicroscopic and Mixed-Species Infections and Multiple Parasite Genotypes

“…Although some of the women may have misreported antimalarial usage or failed to take the drug consistently, the lack of effectiveness is likely due to the high prevalence of multidrug-resistant of P. falciparum parasites in Cameroon. 19,20 Results suggest that immunologic responses, rather than chemoprophylaxis, are responsible for controlling the level of parasitemias in pregnant women.…”

Molecular surveillance of drug-resistant Plasmodium falciparum in two distinct geographical areas of Nigeria

“…Th e limitations of in vivo and in vitro methods for studying drug-resistant malaria and elucidating molecular mechanisms of resistance to some antimalarial drugs have stimulated the widespread use of molecular markers for resistance [15] and RT-PCR fl uorescent dye-based genotyping technologies are now emerging as high-throughput genotyping platforms [16]. In this study, the analysis of the genetic mutations of pfcrt, pfmdr1 and pfdhfr genes in clinical isolates from two geographical locations in Nigeria is described using RT-PCR Fret hybridization and dual labeled probes.…”